Injuries to the central nervous system, including injuries to the spinal cord, are among the most devastating and disabling injuries possible. Depending upon the severity of the injury, paralysis of varying degrees can result. Paraplegia and quadriplegia often result from severe injury to the spinal cord. The resulting effect on the sufferer, be it man or animal, is severe. The sufferer can be reduced to a state of near immobility or worse. For humans, the mental trauma induced by such severe physical disability can be even more devastating than the physical disability itself.
In the mammalian central nervous system (CNS), nerve fibers begin to regenerate after injury or disease, but abruptly stop growing and do not form functional connections. This failure to form neural connections prevents the conduction of nerve impulses through the region of damage, which is the biological basis for the catastrophic behavioral loss after disease or injury to the CNS. A way to overcome this obstacle would be to provide some stimulus to induce significant nerve regeneration in the injured region. While this has been accomplished in limited circumstances in animals by the implantation of peripheral nerve bridges, the delivery of chemical growth factors, such as nerve growth factor (NGF) or brain derived neural growth factor (BDNF), or by the application of an electrical stimulus, each of these methods has serious shortcomings that limit or exclude use in humans. For example, there is no evidence that peripheral bridges actually modify the loss of behavior in animals. It also highly unlikely that surgeons will adopt the use of peripheral bridges, as the technique requires extensive surgery to the spinal cord or brain, risking additional damage. Further, the delivery of growth factors such as NGF and BDNF have been observed to have significant side effects, making patients extremely ill and/or stimulating the growth of latent tumors.
And, although the application of an electrical stimulus, using a technique such as oscillating field stimulation (OFS), has developed into a promising treatment for spinal cord injury, applied voltage also has shortcomings. The OFS procedure only works if the OFS stimulators are implanted within the first three weeks after injury in dogs and animals. It is very clear that the technique does not produce neural regeneration in chronically injured subjects. To date, OFS has failed to produce neural regeneration in over one hundred chronically injured (greater than two months post injury) laboratory guinea pigs (Borgens et al. (1993) Restor Neurol and Neurosci 5, 173-179). The inability to successfully treat chronic CNS injury poses a fundamental challenge, as there are estimated to be approximately 250,000-350,000 persons with longstanding spinal cord injuries.
Accordingly, methods for promoting neural regeneration in CNS injury, particularly in chronic CNS injury, are needed.